Halogenated phosphorus compounds



HALOGENATED PHOSPHORUS COMPOUNDS James Forrest Allen, South Charleston,W. Va., assignor to Food Machinery and Chemical Corporation, New York,N. a corporation of Delaware a No Drawing. Filed Feb. 1, 1956, Ser. No.562,642

17 Claims. (Cl. 260-461) This invention relates to a novel methodof'preparing halogenated phosphorus compounds, and particularly toamethod of preparing novel phosphate esters wherein the halogen atomsare confined to only one of the ester radicals, and wherein at least onehalogen atom is on the alpha carbon atom of the halogenated radical.

This invention relates also to novel halogenated phosphorus compounds,and particularly to novel and useful ortho-phosphate esters having atleast one halogen atom on the alpha carbon atom of an ester radical.Such alphahalogenated compounds are found to show enhanced pesti, cidalactivity compared with the beta-halogenated compounds of the prior art.

The products of the present invention may be illustrated by thefollowing generic formula:

no x

organic radical such as alkyl, substituted alkyl, aralkyl,

aryl and substituted aryl, and Z may be any organic radical such asalkyl, substituted alkyl, aralkyl, ar yl and substituted aryl. R and Rmay be the same or different and may be chlorine, alkoxy, aryloxy,amino, substituted amino, alkylthio and the like. The variety of noveland useful compounds contemplated in this invention is of broad scopedue to the many possible variations among the substituents on the alphacarbon atom. 1

The mainfeatures of the instant invention reside in th provision, forthe first time, of a means. for preparing orthophosphate esters, asdescribed above, whereby the alpha carbon atom is preferentiallyhalogenated. v In addition, this invention provides a novel method "of sobtaining in greatly improved yields certain of those types ofhalogenated phosphate esters for which other means of 3 preparation maytheoretically be possible, but which methods are not efiicient oreconomical. These, and other features, and attendant advantages, willbecome apparent from the subsequent description of this invention.

Prior to the, present invention, certain halogenated phosphates could beobtained'by the additionof halogen to vinyl phosphates. However, theonly types of compounds obtainable by this method arealpha,beta-dihalogen addition products or compounds which contain asmany or more halogen atoms on the beta carbon than on the alpha carbonof the phosphate ester. In addition, this method exhibits otherdisadvantages: the vinyl phosphates are expensive to prepare, andtheryield of halogen addition product is sometimes very low ornon-existent. Representative types of new and 'useful compounds whichmay be prepared by the process of the present invention, and which arenot available from processes ofthe priorart,include the following:-

- I. Phosphate esters having one halogen atom onthe -Patented Aug. 2,1960 alpha carbon of the ester radical and none on the beta carbon, asexemplified by Q? r-o-e-ons '34 H I-I. Phosphate esters having twohalogen atoms onthe alpha carbon ofthe ester radical and none onthJbctzi carbon,asexemplified by gen atoms on the alpha carbon than onthe beta carbon, as exemplified by IV. Phosphate esters having twohalogen atoms on? both the alpha and the beta carbons, as exemplified V.Phosphate esters having difierent halogen atoms in known positions, asexemplified by R 0 Cl Br l o H, a it and R 0 Cl Br i '-ob-on ru 1 1'1VI. Halogenated vinyl phosphates preparedby-dehalogenation ofpolyhalogenated compounds, as exempli fied by p Y Q R 0 c1 01 R o 01 i-O( JHa iI- -O( J=CH: R/ ('31 7 R1 VII. Representative compounds whichtheoretically may be prepared by addition of halogen to vinyl phosphates, but for which the instant invention providesa new and improvedmethod, include phosphate esters having one halogen atom on each of thealpha and beta carbon atoms, as exemplified by 1 I Each of the aboveexamples is illustrative only, and it is obvious that many additionalcombinations and modifi-i cations are within the scope of thisinvention. Also, hy-: drogen atoms in the above formulae may be replaced'by; a large number of organic radicals and substituted organic;radicals.

In these formulae, R and R1 may be the same or differ: out and may behalogen, alkoxy, aryloxy, amino or substi-l tuted amino, alkylthio, orany active hydrogen compound: which may be reacted with aphosphorodihallidate :or monohalidate in the following way:

Thephosphorodihalidates and monohalidates which, are;

obtained in the course of the process of this invention are also novel,active compounds.

In the practice of this invention, the first step is the preparation ofa phosphorodihalidate by methods well '4 with the same or another activehydrogen-containing compound.

Biological data show that the first hydrogen atoms replaced are thoseattached to the alpha carbon atom. For

known in the art, such as the reaction of phosphoryl example, thecompound chloride, bromide or fluoride with an alcohol. In the preferredprocess, reaction with phosphoryl chloride oc- CBHEO 0 Cl ours asexemplified below: {L

These reactions are usually carried out by the gradual addition of thealcohol to an equimolar quantity of phos- P essfmtlauy no msecucldalactlvlty companson the phoryl chloride at temperatures of 0 C. to 50 C,delsomenc compound pending upon the reactivity of the alcohol, and atreduced 0 H o 0 Cl pressure, With vigorous stirring to facilitate theremoval of 2 5 (1} hydrogen chloride. The reaction mixture is thenwarmed -0- s gradually to 5075 C. to complete the reaction and to(3,1150 remove as much hydrogen chloride as possible. The productsobtained from low molecular weight alcohols prepared by the process ofthis invention, has strong inmay be distilled if desired. secticidalproperties.

The next step, the substitution of halogen for hydrogen, Theinsecticidal activity of representative compounds of is a free-radicalcatalyzed reaction. 'Of the many freethe present invention is presentedin Table I below. A radical producing mechanisms which catalyze thisrescreening dosage of 0.125% insecticide was prepared by action,ultraviolet light is used in the preferred process of dissolving thecompound in acetone and diluting to the invention. A mercury vapor lampis a suitable source 0.125% with water. The percent mortality isreported of ultraviolet light, and the reaction is preferably carriedfor the two-spotted spider mite T etranychus bimaculatus out by thegradual addition of halogen, either gaseous or Harvey), Mexican beanbeetle (Epilachna varivestis liquid, to the phosphorodichloridate esterat temperatures Muls.), German roach (Blatella germanica [L.]) and peain the range of about 20-50 C. for the initial phases of aphid(Macrosiphum pisi [Kltb.]

TABLE 1.-INSECTIC]DAL ACTIVITY Percent Mortality at 72 Hours PhosphateTwo- Bean German Pea Spotted Beetle Roach Aphid Mite (C2H5O)2P0)OCHC1CH3 100 100 100 100 CQHEO)QPO)OCCIQCH3 100 100 100 100 CrHsOMPO)OCC12GH@C 100 100 100 100 C2 1 IsO)rP(O)OCHOlGH Br 99 o 0 03)2N)2P(0)OCHC1CH2CI. 94 0 10 0 ((C2H5)2N)2P(O)OCHClCHzCl 100 0 5 55 thereaction. At lower temperatures the reaction is usually too slow to bepractical and at higher temperatures excessive halogen losses and sidereactions may occur. If more than one atom of halogen is to beintroduced into the molecule, or if the organic radical in question isparticularly resistant to halogenation, it may be desirable to operateat somewhat higher temperatures, usually not exceeding about 8-0 C. Thecompletion of the reaction may be noted by the disappearance of thecharacteristic color resulting from the presence of free chlorine orbromine. The products of low to moderate molecular weight can usually bedistilled. The halogenated phosphorodichloridates thus obtained arenovel and useful compounds in themselves.

The halogen atoms attached to phosphorus are very reactive, and a widevariety of compounds may be obtained by reaction with an organiccompound containing an active hydrogen atom. This may be carried out bydissolving the halogenated phosphorodihalidate in an inert solvent suchas hexane or ether, cooling to control the reaction rate, and graduallyadding a mixture of equivalent quantities of the desired compoundcontaining an active hydrogen atom, such as an aliphatic alcohol oramine, and a tertiary base such as pyridine or diethylaniline to absorbliberated hydrogen halide. Alternatively, the phosphorodihalidate may beadded to a solution of the active hydrogen-containing compound and theamine base in an inert solvent. When an amine is one of the reactants,an additional quantity of this amine may be substituted for the tertiarybase. When the addition iscomplete the reaction mixture may be heated tocomplete the reaction. It is also possible to carry out this process intwo steps, obtaining a phosphoromonohalidate which may be reactedfurther The practice of the invention is further illustrated in thefollowing representative examples, wherein parts are by weight unlessotherwise indicated:

EXAMPLE 1 Preparation of l-chloroethyl phosphorodichloridate One hundredsix parts of ethyl phosphorodichloridate was placed in a flask fittedwith a stirrer, Dry Ice condenser, and a graduated addition funnelconnected at the top to a Dry Ice. condenser. Chlorine gas was led intothe Dry Ice condenser connected to the dropping funnel untilapproximately 92.3 parts of liquid chlorine was collected. The liquidchlorine was then introduced in small portions into the ethylphosphorodichloridate under illumination from a mercury vapor lamp. Thetemperature of the reaction mixture was kept at 15-25 C. by externalcooling. Distillation of the product at 1 mm. pressure gave an 18% yieldof l-chloroethyl phosphorodichloridate boiling at 4l-45 C. and having 111.4495. Calcd. for C H Cl O P: C1, 53.9%; P, 15.7%. Found: Cl, 53.6%; P,15.6%.

EXAMPLE 2 Preparation of 1,2-dichlor0ethyl phosphorodichloridate By themethod of Example 1, 2-chloroethyl phosphorodichloridate (0.87 mole),prepared from equimolar quantities of ethylene chlorohydrin andphosphoryl chloride, was chlorinated at 5060 C. with 0.95 mole ofchlorine. Distillation of the product at 1.6 mm. pressure gave a yieldof 1,2-dichloroethyl phosphorodichloridate boiling at 72-73" C. andhaving n 1.4799. Calcd. for C H Cl O P: Cl, 61,492 P, 13.4%. 'Found: C1,60.5%; P, 13.5%.

- v EXAMPLEBY T? dichloridate (0.87 'mole)-was chlorinated at 5065f C. 5

with 1.9 moles of chlorine. Distillation at 1.7 'mm. pressure gave an83% yield of 1,1,2-trichloroethyl "phosphorodichloridate boilingat-;76-7 8,' C. and'havingn 1.4900. Calcd. for C H Cl O P: CI, 66.8%; P,11.7%.

phosphorodichloridate. having n3 1.4980 was obtained and this wasanalyzed without being distilled. Calcd. for C H Cl BrOgP: halogen, 14.5milliequivalents per-*gram; P, 11.2%. Found: halogen, 13.0milliequivalents per gram; P, 11.8%.

EXAMPLE C. for 40 minutes and allowed to stand overnight; Filtration andremoval of solvent in vacuo were followed by Preparation f diethylLz-dichloroefhyl P Q- P distillation of the product at 0.5 mm ofmercury. The Thirty-one and one half parts of absolute ethanol, 54.2 Eof Lz'dichloroethyl tetrijlethylphosphomdiamidate parts pyridine andparts f hexane were placed i boiling at 112133 C. andhavlng 11 1.4651,was 84%. a flask equipped with a sti'rre'rfwater, condenser, and forC10H23C12N2O2Pi C15 23-13%; 102%- addition funnel. With stirringandexternal cooling to Found: C1, 3%; Y i maintain a temperature o C 791parts of Pursuant to tl e requirements of the patentstatutes,'th edichloroethyl phosphorodichloridate, obtained as in Ex- PImZIPIe of smventlon f bienexplamFd and i ample 2, was gradually added. Whenaddition was comfied m so that It can be a gP q k plete stirring wascontinued for 2.5 hoursand the pyriho P1911611; 1111116 chexemphficationncluding dinium chloride then removed by filtration: *kemqvalrof what iscons1dered to represent the best; embodlment of the hexane in vaciloand'd'isfilla'tiofi e p ga'vc the invention. However, 1t should beclearly understood 65.1 parts (76% yield) of diethyl1,2-dichloroethylphos that, Wlthm the Score of the appelldjed 612311118,the Invenphate, boiling at 104-10? (2. at 1.6 mm. of mercury, may bepractlcedvby 3 .skllled m 9 art, and and having zs 14389; CalccL f(36111362041): C1, 40 hav1ng the beneiit of this disclosure, otherwisethan as 28.2%; P, 12.4%. Found: 'Cl, 26.2%; P, 12.9%.speqificallyflswlbed and x mp ifi d mm 1. That which'is claimed a'spatentably novel is: g g V EXAMPLE V 1. The pha-chlorophosphorodichlorida'te'of the fer- I Preparation of diethylJ-ohloroethyl phosphate mula, i it l l-chloroethyl phosphorodichlon'date(0.22 mole) obi f tainedas in Example 1, was reacted with absoluteethanol 7 0.44 mole) and pyrigine 0.44 mole) by the method o( 1 z' U ofExample 5 except at the ethanol and pyridine were Y added to thephosphorodichloridate. Distillation at 1-4 wherem Y 15 selected from thegroup consisting of hydro mm. pressure gave a 47% yieldof diethyll-chloroethyl phosphate boiling at 75-100 C. The fraction analyzedboiled at 92100 C. and had n 1.4199, and d 3 1.1693, Calcd. for C H ClOP: 01, "16.4%; P, 14.3%.;130'11 114: CI, 16.2%; P, 13.7%. .1.5

EXAMPLE 7' 5, j

Preparation of diethyl hexach'loroaciylphosphate Hexachlorooctylphosphorodichloridate (0.27 mole),

6 wereadded at 0 Cf'to a solution ontaining l .l3 'mole' of hexaneand0.28 mole of 1,2-dichloroethyl phosphorof dichloridate, prepared asin Example 1, and the wellstirr ed mixture was allowed to warm slowly to25 C. To the resulting product, ethyl 1,2-dichloroethylphosphorochloridate, was then added 0.28 mole each of pyridine andethylthioethanol, with cooling to maintain the terriperature at 22-30 C.Whenadditionwas complete the reaction mixture was heated to 50 C. for 30minutes and QII 15 659%; -6%- 10 then filtered to remove pyridiniumchloride. The hexane EXAMPLE and other low boiling 'inaterial wereremoved by heata ing to 119 C. at 2.5 mm. of mercury pressure, leavingPreparation of 2-broruo- 1:chloroethyl phosphorodlchlo- 1 6 part5 rarr18%Yield 0f ethyl .ethylthioethyl,l,2-di-..

' "date chloroethyl phosphate. Calcd. for C H Cl O PSi ,iCl,.

One half mole of 2 brornoethyl phosphorodichloridate, 15 P5 109%; l213%; r

obtained from 'equimolar quantities of ethylene bro'mo- 105%; S,

hydrin and phosphoryl chloride, was chlorinated by the I EXAMPLE methodof Example 1 h 055111016 of chlorine at Preparation of 1,2-dichloroethyltetraethylphosphoroai- 20-40 C. A 92% yield of crude2-bromo-'1-chloroethyl 20 ml-date 1 One moleof diethylamine wasgradually added to 0.25 mole of 1,2-dichloroethyl phosphorodichloridatedissolved in 1.9 mole of hexane at about 5? C. over a period of 45minutes. The reaction mixture was then heated to 5 0-60? gen, halogen,alkyl radicals of 1 to 8 carbon atoms and haloalkyl radicals of 1 to 7carbon atoms; and Z is selected from the group consisting'ofalkylradicals of 1 to 8 carbon atoms and haloalkyl radicals of l to '7'carbon 755 2. The alpha-chloro phosphate ester of the formula obtained bthe chlorination of oc l hos horodichl ri- Y date by method of Examine gf 01v 6 d in g whereln Y is selected from the group consisting ofhydrobon tetrachloride (0.52 mole) and to this solution washalogenflalkyl radlcals of 1 to 8 carbon aitoms and added over a'periodof 40 minutesa mixture of ethanol haloalkyl Tadlcals 9 tm Z i (054 mole)and Pym-dine (054 mole) at The from the group consistlng ofalky1rad1cals of 110 8 carreaction mixture was then warmed to 40 C. for.a few hon and'haloalkyl radlcals of 1 to 6.3mm atoms; minutes, filteredto remove the amine salt, and the'solvql i i fi i group i removed invacuo. The yield of crude diethyl hexachlo- .g' g a1 f g a i m carooctyl phosphate, a viscous liquid, was 85%. Calcd. e P am om p OSP acof formula for C H Cl O P: Cl, 45.0%; P, 6.5%. Found: Cl, K3? I 46.7%;P,6.6%. Po-'-o-Y V 7 EXAMPLE 8 R1 fi i p a eihyltzwqhyl g' i e wherein Rand R are each selected from the group cone 5 sisting of loweralkoxy'anddiflower alkyl)amino radi- Absolute ethanol (0.28 mole) andpyridine (0.28 1no1e cals; Y is selected from the group consisting ofhydrogen,

halogen, alkyl radicals of 1 to 8 carbon atoms and haloalkylv radicalsof 1 to 7 carbon atoms; and Z is. selected from the group consisting ofalkyl radicals of 1 to 8 carbon atoms and haloalkyl radicals of 1 to 7carbon atoms; and wherein said alpha-chloro phosphate ester has at leastas many halogen atoms on the alpha carbon as on any carbon atom adjacentto said alphafcarbon. 4. The chlorinated phosphate ester of the formulawherein R and R are lower alkyl radicals and Z is selected from thegroup consisting of alkyl radicals of 1 to 8 carbon atoms and'haloalkylradicals of 1 to 7 carbon atoms.

5. The chlorinated phosphate ester of the formula wherein R and R arelower alkyl radicals and Z is selected from the group consisting ofalkyl radicals of 1 to 8 carbon atoms and haloalkyl radicals of 1 to 7carbon atoms.

6. 1,2-dichloroethyl phosphorodichloridate.

7. 2-bromo-1-chloroethyl phosphorodichloridate.

8. Diethyl l-chloroethyl phosphate.

9. Diethyl 1,1,2-trichloroethyl phosphate.

10. Diethyl 1,1-dichloroethyl phosphate.

11. A pesticidal composition comprising as the essential activeingredient a halogenated phosphate ester as described in claim 3.

12. The process of preparing an alpha-chloro phosphorodichloridate ofthe formula P-O-+Y 01 z wherein Y is selected from the group consistingof hydrogen, halogen, alkyl radicals of 1 to 8 carbon atoms andhaloalkyl radicals of 1 to 7 carbon atoms; and Z is selected from thegroup consisting of alkyl radicals of 1 to 8 carbon atoms and haloalkylradicals of 1 to 7 carbon atoms; comprising: reacting chlorine with aphosphorodichloridate of the formula:

wherein Y and Z are as described, in the presence of a free radicalproducing agent, thereby. producing said alpha-chlorophosphorodichloridate.

13. The process of preparing an alpha-chloro phosphate ester of theformula wherein Y is selected from the group consisting of hydrogen,halogen, alkyl radicals of 1 to 8 carbon atoms and haloalkyl radicals of1 to 7 carbon atoms; Z is selected from the group consisting of alkylradicals of 1 to 8 carbon atoms and haloalkyl radicals of 1 to 7 carbonatoms; and R is' selected from the group consisting of lower alkoxy anddi(lower alkyl)amino radicals; comprising: first reacting chlorine witha phosphorodichloridate of the formula wherein Y is selected from thegroup consisting of hydrogen, halogen, alkyl radicals of 1 to 8 carbonatoms and haloalkyl radicals of 1 to 7 carbon atoms; Z is'selected fromthe group consisting of alkyl radicals of Ho 8 carbon atoms andhaloalkyl radicals of 1 to 7 carbon atoms;

in and R and R are each selected from the group consistingoflower alkoXyand di(lower alkyl)amino radicals; comprisinfifirst reacting chlorinewith a phosphorodichloridate of thefornga wherein Y is selected from thegroup consisting of hydrogen, halogen, alkyl radicals of 1 to 8 carbonatoms and haloalkyl radicals of 1 to 7 carbon atoms; and Z is an alkylradical of 1 to 8 carbon atoms; comprising: reacting chlorine with aphosphorodichloridate of the formula:

wherein Y and Z are as described, in the presence of ultraviolet light,thereby producing said alpha-chloro phosphorodichloridate. V

16. The process of preparing an alpha-chloro phosphorodichloridate oftheformula wherein Y is selected from the group consisting of hydrogen,halogen, alkyl radicals of 1 to 8 carbon atoms and haloalkyl radicals of1 to 7 carbon atoms; and Z is a haloalkyl radical of 1 to 7 carbonatoms; comprising: reactilng chlorine with a phosphorodichloridate ofthe formu a wherein Y and Z are as described, in the presence ofultraviolet light, thereby producing said alpha-chlorophosphorodichloridate.

17. The process of preparing an alpha-chloro phosphorodichloridate ofthe formula wherein Y is Selected from the group consisting of hydrogen,halogen, alkyl radicals of 1 to 8 carbon atoms and haloalkyl radicals of1 to 7 carbon atoms, comprising: reacting chlon'ne with aphosphorodichloridate of the formula wherein Y -is as described, in thepresence of ultraviolet light, thereby producing said alpha-chlorophosphorodichloridate. I

References Cited in the file of this patent UNITED STATES PATENTS2,727,058 Conley Dec. 13, 1955 FOREIGN PATENTS 896,942 Germany Nov. 16,1953 OTHER REFERENCES 4 Perkow et al.: Naturwi'ss," vol. 39, No. 15, p.353

3. THE ALPHA-CHLORO PHOSPHATE ESTER OF THE FORMULA
 14. THE PROCESS OFPREPARING AN ALPHA-CHLORO PHOSPHATE ESTER OF THE FORMULA: